The Genitourinary Cancers Program (GU) is a multidisciplinary research program that includes 17 members from 6 RPCI departments. The overall goal of the GU Program is to translate basic science findings into the clinical setting by identifying novel therapeutic targets and strategies for the prevention and treatment of patients with prostate, kidney and bladder cancer. There are three overarching themes for the GU Program: Theme 1: Genetic and epigenetic signatures; Theme 2: Tumor microenvironment; Theme 3: Novel therapeutic strategies. Program membership spans the breadth of genitourinary cancer and studies highlight investigations on the androgen receptor in prostate cancer, cellular targets in endothelial cells and tumor stem cells in prostate and kidney cancer, new target identification by genetic and epigenetic profiling in renal cell carcinoma and bladder cancer, and the role of vitamin D and broccoli sprout extracts in preclinical and clinical studies for therapy and prevention, respectively in bladder cancer. In addition, the program includes a robust portfolio of clinical studies based on research in the GU program. The GU Program is led by Roberto Pili MD, who has expertise in translational and clinical research in GU malignancies. Dr. Pili's leadership efforts focus on translating novel therapeutic strategies based on preclinical models of prostate, kidney and bladder cancer into clinical testing. The strength of the translational capability of the GU Program is documented by the number of investigator-initiated clinical trials (14) currently accruing across the three disease types. Since the last submission, GU members have authored 365 publications; 19% inter-programmatic collaboration, and 32% intra-programmatic. Current annual total peer-reviewed Program funding is $10.3M, of which $9.0M is NCI, and the total extramural research funding is $11.9M. Weekly seminars, annual research retreats and symposiums foster internal and external collaborations. GU Program members use 13 of the 14 CCSG shared resources and their laboratories contribute to the mentoring of more than twenty pre-doctoral and post-doctoral students from the RPCI Graduate Division. Future plans include expanding the genetic and epigenetic characterization of drug resistant phenotypes across genitourinary cancers and developing novel multimodality, rational combination strategies for the treatment of prostate, kidney and bladder cancer.